Idiopathic focal segmental glomerulosclerosis (FSGS) is a progressive scarring disorder that causes proteinuria and kidney failure in the majority of affected individuals. There is considerable controversy regarding the best therapeutic intervention and the definition of pathological variants of FSGS that may impact therapeutic response rates. This proposal focuses on the design and conduct of a collaborative multicenter trial that will evaluate response rates of children and young adults with the nephrotic syndrome due to FSGS treated with cyclosporin A as compared to corticosteroids plus angiotensin receptor blocker therapy. It will utilize a newly determined FSGS classification scheme as defined by the NY Pathology Consensus Group that includes one of our collaborators. In addition, since incidence of idiopathic FSGS has been increasing over the past 2 decades, a case-control study that will evaluate risk factors for FSGS is proposed to run concurrently with the trial. Our proposed southeastern clinical coordinating center will provide strength to the planned nation-wide trial through our large patient population with FSGS, the strength of the UNC nephropathology service, and the investigators'long track record of clinical trial and epidemiologic research in glomerular diseases through the UNC-Chapel Hill based Glomerular Disease Collaborative Network. In conjunction with committed collaborating sites, our group has over 400 FSGS patients who would be eligible for the proposed trial, as well as established mechanisms for including prospectively identified patients. The proposed case-control study will evaluate risk factors for the development of FSGS such as body mass, birth weight, viral illnesses and smoking in all patients screened for entry into the trial.